Sandbox Reserved 1107: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 12: | Line 12: | ||
<scene name='42/421575/Carbacaprazamycin/1'>Carbacaprazamycin</scene> is a chemically stable analog of caprazamycin nucleoside inhibitors <ref name="more1">DOI:10.1021/id5000376</ref>. One particular characteristic of caprazamycin nucleoside inhibitors is that they have uridine on their structure. It has been shown that Mray inhibitors contains a uridine moiety <ref name="seven">PMID:31266949</ref> | <scene name='42/421575/Carbacaprazamycin/1'>Carbacaprazamycin</scene> is a chemically stable analog of caprazamycin nucleoside inhibitors <ref name="more1">DOI:10.1021/id5000376</ref>. One particular characteristic of caprazamycin nucleoside inhibitors is that they have uridine on their structure. It has been shown that Mray inhibitors contains a uridine moiety <ref name="seven">PMID:31266949</ref> | ||
= Function = | = Function = | ||
| Line 27: | Line 23: | ||
<scene name='42/421575/Carbacaprazamycin/1'>Carbacaprazamycin</scene> is made of uridine, 5-aminoribosyl, diazepanone, and aliphatic tail moieties. The diazepanone ring system makes relatively few interactions with the protein. Carbacapzazamycin contains an uridine binding pocket which is formed by amino acid residues in Loop C ( <scene name='42/421575/Binding_site/1'>G194, L195, and D196</scene>). This pocket is capped off by a π–π stacking interaction with <scene name='42/421575/Binding_site/1'>F262</scene> in Loop D. <scene name='42/421575/Binding_site/1'>K70</scene> forms an additional hydrogen bond with the uracil moiety. Next to the uridine binding site, there is a second binding pocket lined with amino acid residues<scene name='42/421575/Binding_site/1'> T75, N190, D193, and G264</scene>, called the uridine-adjacent pocket. The 5-aminoribose moiety of carbacaprazamycin forms an extensive hydrogen bond network in the uridine-adjacent pocket <ref name="more1"/> <ref name="seven">PMID:31266949</ref>. | <scene name='42/421575/Carbacaprazamycin/1'>Carbacaprazamycin</scene> is made of uridine, 5-aminoribosyl, diazepanone, and aliphatic tail moieties. The diazepanone ring system makes relatively few interactions with the protein. Carbacapzazamycin contains an uridine binding pocket which is formed by amino acid residues in Loop C ( <scene name='42/421575/Binding_site/1'>G194, L195, and D196</scene>). This pocket is capped off by a π–π stacking interaction with <scene name='42/421575/Binding_site/1'>F262</scene> in Loop D. <scene name='42/421575/Binding_site/1'>K70</scene> forms an additional hydrogen bond with the uracil moiety. Next to the uridine binding site, there is a second binding pocket lined with amino acid residues<scene name='42/421575/Binding_site/1'> T75, N190, D193, and G264</scene>, called the uridine-adjacent pocket. The 5-aminoribose moiety of carbacaprazamycin forms an extensive hydrogen bond network in the uridine-adjacent pocket <ref name="more1"/> <ref name="seven">PMID:31266949</ref>. | ||
= Relevance = | |||
Drug resistant bacteria are the cause of death of millions of people worldwide. In the USA alone, hospital infections associated with antibiotic-resistant pathogens cause 99 000 deaths per year<ref name="more2">PMID:30349322</ref>. The development of new antibiotics with new mechanism of action is urgent. Structural analysis of the binding of carbacaprazamycin to MraY provides a better understanding of the chemical logic of MraY inhibition, which can help in the development of novel approaches for the design of antibiotics targeting MraY. | |||
